Cancer, a cell proliferative disorder, is the leading cause of death worldwide. In 1993, Boring et al. estimated approximately 526,000 deaths from cancer alone in the U.S. each year. For example, breast cancer has been the leading cause of death from cancer in woman between the age of 40 and 55. And with increasing pollutions, the incidence of developing ovarian carcinoma, lung cancer, liver cancer and skin cancer has also increased. Studies from Fitzpatrick et al. in 1986 indicated the number of cancer occurrence has increased six times since 1945, revealing the urgent need for a novel method in diagnosis and treatment for cancer.
It was found from the current cancer studies that the senescence, replication and division of eukaryocyte are all regulated by the cell cycle. During a cell replication, chromosome numbers and deoxyribonucleic acid (DNA) content of the cell increased from 2N to 4N in order to produce two daughter cells after cell mitosis, so that each daughter cell has 2N chromosomes. In 1995, Blackburn et al. discovered a repeat sequence at the end of each chromosome, (5′TTAGGG), which is now known as a telomere is shortened after each mitotic cycle. And when the telomere shortens to a critical length, the telomere that covers the terminal end of the chromosome becomes sticky and causes abnormal pairing of the chromosomes and even a cell death in some cases.
In 1995, Feng et al. discovered a high expression of a ribonucleoprotein complex called telomerase that binds on the telomere at the end of the chromosome from the genetic studies of germ-line cells, stem cells, and tumour cells. The role of this telomerase is to maintain the telomere length, preventing the telomere to become shortened after multiple mitoses. The presence of telomerase helps the cell to escape from the cell cycle and become immortal.
Further research on telomerase activity using Telomerase Repeat Amplification Protocol (TRAP), lead to the finding of significant high telomerase activity in tumour cells and in germ cells, whereas almost no telomerase activity is found in normal somatic cells. In 1994 and 1995, Kim and Broccoli et al have also demonstrated an important role of telomerase in controlling apoptotic cascade of tumour cells. Thus, telomerase activity and its expression level are useful in cancer diagnosis and prognosis during cancer treatment due to its high specificity.
On the other hand, based on years of clinical experiences in Chinese medicine, 50 to 60 of Chinese herbs estimated to possess anti-tumour effect are selected using TRAP activity assay. Among these, Panax ginseng, Glycyrrhiza uralensis, Bupleurum scorzonerifolium, Phellodendron amurense, Angelica sinensis, Gentiana scabra, and Scutellaria baicalensis have proved to be very effective in the treatment of malignant tumours. Moreover, in comparison with current anti-cancer drugs, those Chinese herbs have shown less side effects, like reduction in number of white cells, cachexia and so on. Thus, extraction of anti-cancer components from Chinese herbs opens up a new source of novel anti-cancer drug screening.
Further, as an example, paclitaxel injection (commercially known as TAXOL), widely used as a potent chemotherapeutic agent to treat a variety of solid cancers, has a major component of Taxanol which is first isolated from the Pacific yew tree and represented by the following formula: (a molecular formula of C47H51NO14, molecular weight of 854 Da and a diterpene core)

Paclitaxel injection is mainly used in treating ovarian cancer breast cancer metastasis, lung cancer and melanoma via its chemical mechanism of cytotoxicity on tumor cells by inhibiting depolymerization of microtubulin by combining to β-tubulin of cell cytoskeleton in the ratio of 1:1, so as to interrupt cell mitosis and initiate cell death for the tumour cell (Blafosklonny et al., 1995). Therefore, application of Taxane drugs, such as Taxol, is effective in delivering toxicity towards tumour cells at the initial stage of ovarian cancer, improving the survival rate of the patient by about 15% in two years.
However, as the treatment was prolonged, many tumour cells gradually developed drug resistant to Paclitaxel. From the recent research, it was discovered that some of Paclitaxel resistant cells exhibit different β-tubulin expression level and different electrophoresis mobility from the conventional tumour cells. Research works from Rao et al. in 1995 have shown that tumour cells (for example human lung tumour cell lines A549-AT12) are capable of changing their configuration of six β-tubulin subunits to prevent binding with paclitaxel. Instead, paclitaxel is discharged out of the cell through ion pumping, making the tumour cells drug-resistant to paclitaxel after a period of chemotherapy.
Also, other anti-cancer agents such as 5-fluorouracil, epothilone, cisdiammine dichloroplatinum (Cisplatin), procarbazine and cyclophosphamide when clinically used alone or in conjunction with paclitaxel cannot provide a satisfactory outcome in terms of killing the cancer cells developed with drug resistant to paclitaxel. Results from cell culture experiment also indicate that it is difficult to effectively inhibit proliferation of Paclitaxel-resistant tumour cells using current anti-cancer drugs. In order to achieve a higher efficacy, it is often necessary to increase the administering dosage. For example, in an animal experiment, a rat may be injected with 300 mg/kg of paclitaxel. However this would result in high degree of necrosis for the normal cells due to its strong cytotoxicity possessed by the drug.
Thus, in order to improve the cytotoxic effect towards tumour cells at latter stages of chemotherapy, it is imperative to find and isolate anti-cancer components from Chinese herbs that have previously shown promising result in the treatment of cancer to effectively suppress proliferation of Paclitaxel-resistant tumour cell lines.